Contents
Introduction
Von Willebrand’s Disease (vWD) is a type of haemophilia (clotting disorder). It is caused by deficiencies in a protein called von Willebrand factor (vWF), which helps to prolong the life of factor VIII in the clotting cascade. Most cases are relatively mild, and the vast majority probably go undiagnosed.
- Asymptomatic deficiencies affect 1% of general population
- Symptomatic disease affects 100 per million
von Willebrand’s disease is the most common inherited bleeding disorder (coagulopathy)
- Other examples include haemophilia A and haemophilia B
- Haemophilia A is caused by deficiencies in factor VIII itself
- Haemophilia B affects factor IX
It was first described in 1926 by Erik von Willebrand – working on remote islands between Sweden and Finland, as is also sometimes known as vascular haemophilia.
There are three types of vWD – types 1, 2 and 3.
Epidemiology
- Prevalence of 1-2% in the general population
- More common in females
- More common with blood type O
- Most patients have mild disease
Presentation
Variable – depends on the extent of the disease:
- Bleeding for mucosa
- Epistaxis
- Menorrhagia (consider vWD in women with menorrhagia and no identified gynaecological cause)
- Spontaneous bleeding
- Including into joints or other internal organs
- Severe vWD: spontaneous mucosal bleeding, death secondary to massive GI haemorrhage
Pathology
vWD results from defects in von Willebrand factor – vWF
- vWF important in platelet adhesion and factor VIII transport
- vWF helps to attract circulating platelets to the site of bleeding
- It binds to factor VIII and prevents it being cleared from plasma
- You might want to brush on the clotting cascade!
Types of vWD
Type 1
- Decreased concentration of vWF
- 80% of cases of vWD
- Often autosomal dominant
- Levels of vWF can be measured – and disease severity correlates to levels – “quantitative deficiency“
- Normal lifespan
- Occasional easy bruising
- May have increased risk of bleeding after dental procedures and surgery
Type 2
- “Qualitative deficiency” – normal quantities if vWF produced – but it is defective
- Autosomal dominant or Autosomal recessive inheritance
- 20-30% of cases of vWD
- Subclassified according to the defect in the vWF:
- 2a – lack of high molecular weight vWF
- 2b – defective adhesion due to increased binding
- 2m – decreased platelet dependent vWF function
- 2n – failure to bind factor VIII
- Bleeding tendency varies depending on the type
Type 3
- Near complete absence of vWF
- 1-5% of cases
- Autosomal recessive inheritance
- Mimics haemophilia
- Severe mucosal bleeding
- May present with severe haemarthrosis (bleeding into the joints)
Investigations
Many patients with mild disease will go undiagnosed. Patients with abnormal bleeding will typically present as a result of their bleeding, and should be investigated.
- Blood count normal except for a moderate reduction in platelets in some with type 2
- Most patients have normal platelet count
- APTT prolonged
- PT usually normal
- Diagnosis: quantitative immunoassay/functional assay of vWF, electrophoresis
- Interpret vWF levels with blood group (usually lower in blood group O)
- Will typically be reported as a qualitative or quantitative deficiency
- Factor VIII level
- Usually low – vWF prolongs the life of factor VIII in the blood
- Offer screening to all first-degree relatives – regardless of their bleeding history
Management
- Avoid NSAIDs and anti platelet drugs
- Minor bleeds don’t require any specific treatment
- More severe bleeds may be treated with:
- Local measures (pressure)
- Tranexamic acid – can be given orally. Also available as a mouthwash, and IV infusion for severe cases
- Desmopressin (DDAVP)
- Used in severe bleeds
- Can be given IV or intranasally
- Consider COCP in women with menorrhagia
- Factor VIII concentrates with vWF may be given
- Consider platelet infusion for patients who aren’t responsive to other treatment
References
- Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
- Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
- Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy
- von Willebrand’s disease – patient.info